From molecular signatures to radiomics: tailoring neurooncological strategies through forecasting of glioma growth.

OBJECTIVE: Contemporary oncological paradigms for adjuvant treatment of low- and intermediate-grade gliomas are often guided by a limited array of parameters, overlooking the dynamic nature of the disease. The authors' aim was to develop a comprehensive multivariate glioma growth model based on multicentric data, to facilitate more individualized therapeutic strategies. METHODS: Random slope models with subject-specific random intercepts were fitted to a retrospective cohort of grade II and III gliomas from the database at Kepler University Hospital (n = 191) to predict future mean tumor diameters. Deep learning-based radiomics was used together with a comprehensive clinical dataset and evaluated on an external prospectively collected validation cohort from University Hospital Zurich (n = 9). Prediction quality was assessed via mean squared prediction error. RESULTS: A mean squared prediction error of 0.58 cm for the external validation cohort was achieved, indicating very good prognostic value. The mean ± SD time to adjuvant therapy was 28.7 ± 43.3 months and 16.1 ± 14.6 months for the training and validation cohort, respectively, with a mean of 6.2 ± 5 and 3.6 ± 0.7, respectively, for number of observations. The observed mean tumor diameter per year was 0.38 cm (95% CI 0.25-0.51) for the training cohort, and 1.02 cm (95% CI 0.78-2.82) for the validation cohort. Glioma of the superior frontal gyrus showed a higher rate of tumor growth than insular glioma. Oligodendroglioma showed less pronounced growth, anaplastic astrocytoma-unlike anaplastic oligodendroglioma-was associated with faster tumor growth. Unlike the impact of extent of resection, isocitrate dehydrogenase (IDH) had negligible influence on tumor growth. Inclusion of radiomics variables significantly enhanced the prediction performance of the random slope model used. CONCLUSIONS: The authors developed an advanced statistical model to predict tumor volumes both pre- and postoperatively, using comprehensive data prior to the initiation of adjuvant therapy. Using radiomics enhanced the precision of the prediction models. Whereas tumor extent of resection and topology emerged as influential factors in tumor growth, the IDH status did not. This study emphasizes the imperative of advanced computational methods in refining personalized low-grade glioma treatment, advocating a move beyond traditional paradigms.

Detection of interictal epileptiform discharges in an extended scalp EEG array and high-density EEG-A prospective multicenter study.

OBJECTIVES: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). METHODS: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. RESULTS: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. SIGNIFICANCE: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

Advanced birefringence measurements in standard terahertz time-domain spectroscopy.

Polarization-sensitive (PS) terahertz (THz) technology can be used for investigating anisotropic materials that are opaque for visible light. A full characterization of an anisotropic material requires the extraction of the birefringence as well as the orientation of the optical axis from the measurement data. We present an approach based on THz time-domain spectroscopy (TDS) that exploits the spectral content of the THz signal for determining these two parameters from only two measurements. In contrast to an earlier approach with a more sophisticated PS-THz system and quasi-circularly polarized THz radiation, now a simple standard THz-TDS system can be employed. After a description of the mathematical model for data analysis we demonstrate the applicability of our method for a lithium niobate crystal and furthermore for a glass-fiber reinforced polymer sample, for which the orientation of the optical axis and birefringence are obtained in a spatially resolved way, showing the potential of the method also for PS-THz imaging. As no specialized setup or components are required, our approach can be easily and extensively applied for the analysis of anisotropic samples at THz frequencies.

Polarization sensitive terahertz imaging: detection of birefringence and optical axis.

We present a practicable way to take advantage of the spectral information contained in a broadband terahertz pulse for the determination of birefringence and orientation of the optical axis in a glass fiber reinforced polymer with a single measurement. Our setup employs circularly polarized terahertz waves and a polarization-sensitive detector to measure both components of the electromagnetic field simultaneously. The anisotropic optical parameters are obtained from an analysis of the phase and frequency resolved components of the terahertz field. This method shows a high tolerance against the skew of the detection axes and is also independent of a reference measurement.

Efficient terahertz en-face imaging.

In this work, we develop a pulsed terahertz imaging system in reflection geometry, where due to scanning of the terahertz beam neither the sample nor the emitter and detector have to be moved. We use a two mirror galvanoscanner for deflecting the beam, in combination with a single rotationally symmetric focusing lens. In order to efficiently image planar structures, we develop an advanced scanning routine that resolves all bending effects of the imaging plane already during measurement. Thus, the measurement time is reduced, and efficient imaging of surfaces and interfaces becomes possible. We demonstrate the potential of this method in particular for a plastic-metal composite sample, for which non-destructive evaluation of an interface is performed.

Force-induced lysozyme--HyHEL5 antibody dissociation and its analysis by means of a cooperative binding model.

Dynamic force spectroscopy probes the kinetic properties of molecules interacting with each other such as antibody-antigen, receptor-ligand, etc. In this article, a statistical model for the dissociation of such cooperative systems is presented. The partner molecules are assumed to be linked by a number of relatively weak bonds that can be grouped together into cooperative units. Single bonds are assumed to open and close statistically. Our model was used to analyze molecular recognition experiments of single receptor-ligand pairs in which the two molecules are brought into contact using an atomic force microscope, which leads to the formation of a strong and specific bond. Then a prescribed time-dependent force is applied to the complex and the statistical distribution of forces needed to pull the molecules completely apart is measured. This quantity is also calculated from our model. Furthermore, its dependence on the model parameters, such as binding free energy, number of bonds and groups, number of cooperative elementary bonds and degree of cooperativity within a group, influence of the force on the binding free energy, and the rate of change of the pulling force, is determined.

Design and characterization of telecentric f-θ scanning lenses for broadband terahertz frequency systems.

Telecentric beam scanning using f-θ lenses offers nearly uniform spot size, linear beam displacement, and normal incidence angle over a planar surface. These unique properties allow for the minimization of imaging distortion over a wide field-of-view. In this article, we present a numerical method for designing custom f-θ lenses in the THz regime. We fabricated three lenses made from different commonly used polymer materials in the THz optics. We demonstrated their optical performance metrics compared to a conventional plano-convex lens over the broadband 0.3 THz-1 THz range. We find that the f-θ lens designed using the optical properties of high-density polyethylene achieved superior performance by maintaining a constant phase over a wide field of view of about 34°. We demonstrate this isophase property by measuring a constant time of arrival of the THz time-domain pulses over a reference mirror with a standard deviation of ∼19 fs, in excellent agreement with simulation predictions. This work will pave the way for the design and implementation of highly precise and fast telecentric imaging systems in the THz frequencies.

Terahertz time-domain spectroscopy for monitoring the curing of dental composites.

We apply terahertz (THz) time-domain spectroscopy for monitoring the curing process of three different light-curing dental composites. Exact knowledge of the sample thickness is required for a precise determination of the THz dielectric parameters, as the materials exhibit shrinkage when they are cured. We find very small but significant changes of the THz refractive index and absorption coefficient during stepwise light exposure. The changes in the refractive index are correlated with changes in the density of the materials. Furthermore, the refractive index and the sample thickness are found to give the most reliable result for monitoring the curing process of the dental composites.